Helicobacter pylori and gastric cancer

doi:10.1016/S0002-9343(98)00393-3

The American Journal of Medicine

Volume 106, Issue 2, February 1999, Pages 222-226

https://doi.org/10.1016/S0002-9343(98)00393-3 Get rights and content

Abstract

Infection with Helicobacter pylori is now recognized as the primary cause of peptic ulcers and their recurrence. Compelling evidence has also been found linking H pylori infection to gastric cancer, the second most common cancer in the world. Given the high rate of patient morbidity and mortality associated with gastric cancer, any method by which one can reduce the occurrence of the disease or increase its early detection is desirable. The strong correlation with H pylori infection and the current availability of easily administered tests for the detection of the pathogen argue for screening at least those individuals with a family history of gastric cancer or other risk factors. This article reviews the association between H pylori and gastric cancer and the pathologic changes that the infection produces in the gastric mucosa, as well as the cost-effectiveness of universal testing and eradication of the infection in H pylori–positive individuals to reduce gastric cancer.

Section snippets

The association between H pylori and gastric cancer

The first compelling evidence linking H pylori infection to gastric carcinoma was generated by seroepidemiologic studies using a nested case-control design in the United States and Britain 4, 5, 6. These studies used previously recorded medical history and stored sera from a large cohort of subjects. Those who developed gastric malignancy were compared with control subjects without gastric carcinoma; sera from each set of subjects were tested for the presence of IgG antibodies to H pylori.

Chronic atrophic gastritis and H pylori

Because atrophic gastritis is found in 80% to 90% of patients with gastric carcinoma, it is commonly believed to be etiologically related to this malignancy (18). Chronic atrophic gastritis is nearly universal in the populations at highest risk for gastric cancer (19). Approximately 10% of patients with chronic atrophic gastritis will develop gastric carcinoma during a 15-year period 18, 20, 21, 22. By contrast, among patients with normal gastric mucosa or only superficial gastritis, none

Mechanism of H pylori carcinogenesis

Chronic epithelial injury can cause tumorigenesis in many tissues. In the gastrointestinal tract, inflammation has been linked not only to gastric malignancy, but also to cancers in the esophagus (reflux disease and Barrett’s esophagus), small bowel (Crohn’s disease and adenocarcinoma), and colon (inflammatory bowel disease and adenocarcinoma).

H pylori is a gram-negative spiral shaped organism that colonizes gastric type epithelium. The organism adheres only to gastric surface mucous cells and

Can eradication of H pylori prevent gastric cancer?

The inflammation caused by H pylori infection will gradually reverse after eradication of the organism. Further, the prevalence of atrophy is very low in those without inflammation. Yet, whether eradication of H pylori can prevent gastric atrophy and whether this in turn will prevent gastric cancer is not known. Some reports have described regression of preneoplastic changes, such as atrophy or reversal of intestinal metaplasia, with H pylori treatment 42, 43, 44, 45. Uemura et al (46) reported

Cost-effectiveness of H pylori eradication for gastric cancer prevention

Recognition of the potential role of H pylori in carcinogenesis raises the issue of whether the entire population should be screened and treated for the infection with the goal of reducing death from gastric cancer. Caution has been raised regarding this issue, as it is possible that the remarkable survival of H pylori through human evolution suggests some unrecognized benefit to the host. However, assuming H pylori provides no benefit, is it rational to eradicate an infection with the hopes of

Conclusion

The recognition of a bacterial cause of inflammatory precursors to gastric cancer represents a potential opportunity for chemoprevention, especially if low-cost diagnostic tests for H pylori infection and effective, nontoxic therapies are available. The results from two pharmacoeconomic models suggest that further research is critical to address whether H pylori eradication will have public health benefits. Screening the entire population would be quite expensive, yet identification of

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In order to explore the etiology of gastric cancer on global gene expression level, we developed advanced bioinformatic analysis to investigate the variations of global gene expression and the interactions among them.
We downloaded the dataset GSE63288 from Gene Expression Omnibus (GEO) database which included 22 human gastric cancer and 22 healthy control samples. We identified the differential expression genes, and explored the Gene ontology (GO) and pathways of the differentially expressed genes. Furthermore, integrative interaction network and co-expression network were employed to identify the key genes which may contribute to gastric cancer progression.
The results indicated that 5 kinases including BUB1, TTK protein kinase, Citron Rho-interacting kinase (CIT), ZAK and NEK2 were upregulated in gastric cancer. Interestingly, BUB1, TTK, CIT and NEK2 have shown high expression similarities and bound with each other, and participated in multiple phases of mitosis. Moreover, a subnet of co-expression genes e.g. KIF14, PRC1, CENPF and CENPI was also involved in mitosis which was functionally coupled with the kinases above. By validation assays, the results indicated that CIT, PRC1, TTK and KIF14 were significantly upregulated in gastric cancer.
These evidences have suggested that aberrant expression of these genes may drive gastric cancer including progression, invasion and metastasis. Although the causal relationships between gastric cancer and the genes are still lacking, it was reasonable to take them as biomarkers for diagnosis of gastric cancer.
Coexistence of gastrointestinal stromal tumours (GIST) and malignant neoplasms of different origin: Prognostic implications
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Miettinen et al. have reported a non-random and statistically association of GIST and acute myeloid leukaemia [72]. Regarding the Helicobacter pylori infection, although it has been implicated as a carcinogen of the stomach by the World Health Organization in 1994 [73] and strongly associated with gastric MALT lymphoma [74,75] at present, there is no evidence that links GIST development to H. pylori infection. Apart from the above mentioned theories, simple coincidence could also be the case, especially in centres having high incidence rates of gastric surgery [29.32].
Over the past decade, several changes occurred in diagnostics, treatment and understanding of pathogenesis of gastrointestinal stromal tumours (GIST). However, their coexistence with other malignancies of different histogenetic origin remains a challenging issue.
Patients diagnosed with GIST in a 10-years period were identified retrospectively and clinical history and findings thoroughly explored for the presence of associated other malignancies. Follow up data were obtained and analysed for prognostic impact of the concurrent malignancy and/or GIST.
Thirty seven (27 males, 10 females) of 86 GIST-patients (43%) had another malignancy. Mean age was 70 years. Associated malignancies were gastrointestinal (n = 29; 69%), renal-/urological (n = 5; 12%), haematological (n = 4; 9.5%), cutaneous (n = 3; 7%) and thyroid (n = 1; 2.5%) in origin. Majority of GISTs occurred in stomach (65%) and small intestine (30.6%) and most (78%) were asymptomatic incidental findings during diagnostic or therapeutic procedures for associated malignancies. GIST size ranged from 0.1 cm to 9 cm (mean, 2.2 cm) and all of them had a low (<5/50HPFs) or no mitotic activity. Thirty-one tumours (84%) were of no/very low/low risk and 6 were of intermediate risk. During follow-up (range 3–160 months, mean; 60 months), one patient suffered from distant metastases of GIST. Seven patients (19%) died of associated malignancies and three patients (8%) of other non-tumour-associated cause, but none died of GIST.
Coexistence of GIST with other malignancies is higher than previously reported and should draw attention of clinicians towards these incidental findings. Prognosis in these patients is usually determined by other malignancy and not significantly influenced by GIST. Therefore treatment algorithms should be focused on prognostically relevant malignancy.
The clinical evaluation of abdominal pain in adults
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Treatment of Helicobacter reduces the incidence of ulcer recurrence. Helicobacter is found in 65–95% of patients with gastric ulcers and 70–90% of patients with gastric cancer.4 However, Helicobacter eradication has not been proven to reduce gastric adenocarcinoma risk, although mucosa-associated lymphoid tissue type lymphomas (MALT-lymphoma) may achieve remission following Helicobacter eradication.5
Abdominal pain represents a diagnostic and therapeutic challenge for the gastroenterologist and the general physician. An accurate history and diagnostic framework are essential to ensure that serious physical illness is not missed, and that psychological causes of abdominal pain are not reinforced by excessive investigation. Understanding of the pathophysiology of abdominal pain, and its common presentations, allows the skilled physician to quickly establish the diagnosis. Visceral pain is typically poorly localized, unlike somatic pain, which is well localized and sharp in nature, typically reflecting inflammation of the pleura, peritoneum or diaphragm. Referred pain is felt distant from the affected organ due to activation of dermatomal somatic nerves. This article focuses on the diagnosis and management of acute abdominal pain, and explains common presentations, including hepatobiliary, epigastric, pancreatic and lower abdominal pain. Although in most cases this diagnostic approach will provide the physician with the likely diagnosis, there are several groups of patients, including the elderly and immunosuppressed, in whom this approach is inadequate. By being alert to the atypical presentations described, these challenging patients can be successfully managed.
Identification of volatile organic compounds secreted from cancer tissues and bacterial cultures
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The early cancer diagnosis increases the possibility of total recovery. The infection of Helicobacter pylori is associated with gastric cancer, the second most common cancer in the world. The determination of volatile organic compounds (VOCs) excreted by stomach tissue and bacteria culture has been investigated. Solid-phase microextraction (SPME) was used for preconcentration and the determination was accomplished by gas chromatography coupled with mass spectrometry (GC/MS). The samples of tissue were taken from five patients (ten samples) with stomach cancer and normal (non-cancerous) segments from other parts of the stomach were used as a control. Eighteen compounds were identified in stomach tissue and seven of them were present both in healthy and cancer tissue. These compounds assumed to be endogenous and acetone ratio (AR) was calculated for ethanol, butane, carbon disulfide, 1-propanol, 2-butanone and 2-pentanone. The data shows that amount of 1-propanol and carbon disulfide in the gaseous composition is higher in cancer tissue than in normal tissue. Eight compounds were identified both in bacteria and tissue. These data suggest that bacteria present in the stomach might cause the increase in the concentration of 1-propanol and carbon disulfide in emission from cancer tissue.
A Case Study on Modeling the Time to Recurrence of Gastric Cancer Patients
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ReviewsHelicobacter pylori and gastric cancer

Abstract

Section snippets

The association between H pylori and gastric cancer

Chronic atrophic gastritis and H pylori

Mechanism of H pylori carcinogenesis

Can eradication of H pylori prevent gastric cancer?

Cost-effectiveness of H pylori eradication for gastric cancer prevention

Conclusion

Lancet

Gastroenterology

Lancet

Gastroenterology

Gastroenterology

Gastroenterology

Cancer Lett

Gastroenterology

Lancet

Gastroenterology

The decline in gastric cancer; epidemiology of an unplanned triumph

Epidemiol Rev

Estimates of the worldwide incidence frequency of eighteen major cancers in 1985

Int J Cancer

Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii

NEJM

Helicobacter pylori infection and the risk of gastric carcinoma

NEJM

Association between infection with Helicobacter pylori and the risk of gastric cancer

BMJ

An international association between Helicobacter pylori infection and gastric cancer

Lancet

Helicobacter pylori infection and gastric lymphoma

NEJM

Gastric MALT lymphoma and Helicobacter pylori

Yale J Biol Med

Cure of Helicobacter pylori infection and duration of remission of low-grade gastric mucosa-associated lymphoid tissue lymphoma

J Nat Canc Inst

Is there a causal relationship between H. pylori infection and gastric maltoma? A meta-analysis of evidence from epidemiological studies and clinical trials

Gut

Consensus conference. Medical treatment of peptic ulcer disease. Practice guidelines. Practice Parameters Committee of the American College of Gastroenterology

JAMA

Current European concepts in the management of Helicobacter pylori infection—the Maastricht Consensus Report

Gut

The risk of stomach cancer in patients with gastric cancer or duodenal ulcer disease

NEJM

Atrophic gastritis

Precancerous gastric lesions in a population at high risk of stomach cancer

Cancer Res

Simple atrophic gastritis and gastric cancer

Gut

Reviews
Helicobacter pylori and gastric cancer